The pharmacokinetics of desmethylmisonidazole (DESMISO, NSC-261036) was studied in 84 patients and the results compared with a previous clinical study of misonidazole (MISO, NSC-261037) to determine relationships between neurotoxicity and pharmacokinetic parameters. The dose of DESMISO ranged from 0.9 g/meter squared to 4 g/meter squared. DESMISO has a plasma elimination half-life of 6.0 + or - 0.6 hr and an apparent distribution volume of 45 + or - 2L. A one hour DESMISO plasma level of 38 + or - 3 microgram/ml per g/meter squared dose was observed and 60 + or - 7% of the parent compound was recovered in patients' urine. A correlation between the incidence of neurotoxicity and the DESMISO plasma x concentration curve was observed similar to that found for MISO; DESMISO is approximately twice as toxic as MISO when compared in this manner. The disposition of riboxamide (NSC-286193) was studied in mice at doses of 25 and 250 mg/kg. At 250 mg/kg, an initial plasma concentration of 1.38 mM was found which declined with an initial T 1/2 of 21 minutes and exhibited a terminal T 1/2 of 260 minutes. The amount of circulating metabolites was less than 5% of the circulating radioactivity. The steady state volume of distribution is more than 300 x the total mouse volume indicating that the drug is bound, sequestered, and/or metabolized.